Introduction: The purpose of this study was to illustrate the potential costs and health consequences of implementing advanced CT angiography and perfusion (CTAP) as the initial imaging in patients presenting with acute ischemic stroke (AIS) symptoms at a comprehensive stroke center (CSC).Methods: A decision-simulation model based on the American Heart Association's recommendations for AIS care pathways was developed to assess imaging strategies for a 5-year period from the institutional perspective. The following strategies were compared: (1) advanced CTAP imaging: NCCT + CTA + CT perfusion at the time of presentation; (2) standard-of-care: non-contrast CT (NCCT) at the time of presentation, with CT angiography (CTA) ± CT perfusion only in select patients (initial imaging to exclude hemorrhage and extensive ischemia) for mechanical thrombectomy (MT) evaluation. Model parameters were defined with evidence-based data. Cost-consequence and sensitivity analyses were performed. The modified Rankin Scale (mRS) at 90 days was used as the outcome measure.Results: The decision-simulation modeling revealed that adoption of the advanced CTAP imaging increased per-patient imaging costs by 1.19% ($9.28/$779.72), increased per-patient treatment costs by 33.25% ($729.96/$2,195.24), and decreased other per-patient acute care costs by 0.7% (–$114.12/$16,285.85). The large increase in treatment costs was caused by higher proportion of patients being treated. However, improved outcomes lowered the other per-patient acute care costs. Over the five-year period, advanced CTAP imaging led to 1.63% (66/4,040) more patients with good outcomes (90-day mRS 0-2), 2.23% (66/2,960) fewer patients with poor outcomes (90-day mRS 3-5), and no change in mortality (90-day mRS 6). Our CT equipment utilization analysis showed that the demand for CT equipment in terms of scanner time (minutes) was 24% lower in the advanced CTAP imaging strategy compared to the standard-of-care strategy. The number of EVT procedures performed at the CSC may increase by 50%.Conclusions: Our study reveals that adoption of advanced CTAP imaging at presentation increases the demand for treatment of acute ischemic stroke patients as more patients are diagnosed within the treatment time window compared to standard-of-care imaging. Advanced imaging also leads to more patients with good functional outcomes and fewer patients with dependent functional status.

Advancements in sequencing have led to the proliferation of multi-omic profiles of human cells under different conditions and perturbations. In addition, several databases have amassed information about pathways and gene “signatures” – patterns of gene expression associated with specific cellular and phenotypic contexts. An important current challenge in systems biology is to leverage such knowledge about gene coordination to maximize the predictive power and generalization of models applied to high-throughput datasets. However, few such integrative approaches exist that also provide interpretable results quantifying the importance of individual genes and pathways to model accuracy. We introduce AKLI-MATE, a first kernel-based stacked learner that seamlessly incorporates multi-omics feature data with prior information in the form of pathways for either regression or classification tasks. AKLIMATE uses a novel multiple-kernel learning framework where individual kernels capture the prediction propensities recorded in random forests, each built from a specific pathway gene set that integrates all omics data for its member genes. AKLIMATE outperforms state-of-the-art methods on diverse phenotype learning tasks, including predicting microsatellite instability in endometrial and colorectal cancer, survival in breast cancer, and cell line response to gene knockdowns. We show how AKLIMATE is able to connect feature data across data platforms through their common pathways to identify examples of several known and novel contributors of cancer and synthetic lethality.

Background: Global metabolic dysfunction-associated steatotic liver disease (MASLD) prevalence is estimated at 30% and projected to reach 55.7% by 2040. In the Veterans Affairs (VA) healthcare system, an estimated 1.8 million veterans have metabolic dysfunction-associated steatohepatitis (MASH). Methods: Adult patients at risk for MASLD in a VA healthcare system underwent Fibrosis-4 (FIB-4) and Enhanced Liver Fibrosis (ELF®) testing. Referral rates and cost savings were compared among 6 noninvasive testing (NIT) strategies using these 2 tests independently or sequentially at various cutoffs. Results: Enrolled patients (N = 254) had a mean age of 65.3 ± 9.3 years and mean body mass index (BMI) of 31.7 ± 6, 87.4% male: 78.3% were non-Hispanic/Latino, and 96.5% had type 2 diabetes mellitus (T2DM). Among the 6 evaluated strategies, using FIB-4 followed by ELF at a 9.8 cutoff yielded the highest proportion of patients retained in primary care without need of referral to hepatology clinic (165/227; 72.7%), and was associated with the lowest costs ($407.62). Compared to the FIB-4 only strategy, FIB-4/ELF with a 9.8 cutoff strategy resulted in 26% fewer referrals and 8.47% lower costs. In the subgroup of patients with BMI >32, there were 25.17% fewer referrals and costs were 8.31% lower. Conclusions: Our study suggests that sequential use of ELF with a 9.8 cutoff following indeterminate FIB-4 tests results in lower referral rates and lower care costs in a veteran population at risk of MASLD. Adding ELF as a sequential test after indeterminate FIB-4 might help reduce the number of referrals and overall cost of care.